1. Field
Integrated tissue processing and embedding systems, and methods.
2. Background Information
Histology is a science or discipline associated with the processing of tissue for examination or analysis. The examination or analysis may be of the cellular morphology, chemical composition, tissue structure or composition, or other tissue characteristics. Histology is used in research, diagnostic, and other applications.
FIG. 1 is a block flow diagram of an embodiment of histological method 100. This is just one representative histological method. Various modifications of this histological method exist, such as by adding, removing, and/or rearranging operations.
At block 101, grossing and fixation may be performed on tissue. The tissue may represent tissue samples or specimens taken during biopsies, autopsies, surgeries, or other tissue extractions. The tissue may also represent a pellet of tissue. Grossing the tissue may potentially include examining the tissue, describing the tissue, and trimming the tissue to an appropriate size and/or shape. Fixing or fixating the tissue may include placing the grossed tissue in a fixative solution, which may help to preserve the tissue and/or prevent decomposition.
After grossing and fixation, tissue processing may be performed on the tissue, at block 102. During tissue processing, the tissue may be dried or dehydrated by removing most or almost all of the water from the tissue. Commonly, such drying may be achieved by exposing the tissue to one or more dehydrating agents. After drying the tissue, clearing of the dehydrating agents may optionally be performed, and then wax (e.g., paraffin), wax with added plasticizers, or another embedding agent may be introduced or infiltrated into the dried tissue. In some cases, a vacuum may be applied to assist with infiltration of the wax or other embedding agent into the tissue.
As will be explained further below, it is common in histology to cut the tissue into a thin section, for example with a microtome. Cutting a tissue that has not undergone tissue processing may tend to be challenging. Without tissue processing, the tissue may be soft and filled with water. Force exerted on the tissue by a blade that is used to cut the tissue into the thin sections may tend to compress the tissue and force some of the water out of the tissue. The tissue may not fully decompress after removal of the blade. This may tend to alter the structure of the tissue, which in some cases may tend to hinder examination or analysis. However, removing the water from the tissue, and infiltrating wax or another embedding agent into the tissue (e.g., infiltrating into interstices of the tissue), may help to allow the tissue to be cut with less compression and/or alteration of the tissue structure.
After tissue processing, embedding may be performed on the tissue, at block 103. During embedding, the tissue that has been dried and infiltrated with wax or another embedding agent during tissue processing may be embedded in a block or other mass of wax, various polymers, or another embedding medium. Representatively, the dried and wax-infiltrated tissue may be placed in a mold, melted wax may be dispensed over the tissue until the mold has been filled with the wax, and then the wax may be cooled and hardened. Embedding the tissue in the block of wax may help to provide additional support during cutting or sectioning of the tissue.
After embedding, the tissue embedded in the block of wax may be sectioned into thin tissue sections, at block 104. During sectioning a microtome or other bladed instrument may be used to cut the tissue embedded in the block of wax into the thin sections. By way of example, the thickness of the tissue sections may range from about one to ten microns. The sections, or a ribbon of multiple sequentially cut sections, may be floated on warm water, or otherwise softened and flattened, and then placed on microscope slides and allowed to dry.
After sectioning, the wax is removed and the thin tissue sections may be stained, at block 105. During staining, the tissue sections may be exposed to various stains. The stains may combine with the tissue sections to provide contrast between tissue components, structures, molecules, or some combination thereof, depending upon the particular stains. Some stains combine non-specifically chemically with the tissue, whereas other stains combine specifically with certain bacteria types, enzymes, molecules, portions of molecules, etc.
After staining, coverslipping may be performed, at block 106. During coverslipping, a protective transparent cover may be applied over the stained tissue section. Coverslipping may aid in microscopic evaluation and/or may help to protect the tissue section from exposure to air and subsequent handling.
Currently, tissue processing is often performed automatically by an instrument known as an automated tissue processor. Likewise, embedding is often performed automatically by an instrument known as an automated embedding system. However, the automated tissue processor and the automated embedding system are currently separate, unconnected instruments.
Accordingly, after tissue processing has been performed, the tissue that has been dried and infiltrated with wax or another embedding agent needs to be manually removed from the automated tissue processor, moved to, and introduced into the automated embedding system before embedding may begin. Despite the automation within each of the separate instruments, manual unloading, transfer, and loading of tissue from the automated tissue processor to the automated embedding system is necessary.
Performing such operations manually tends to unnecessarily occupy the time of laboratory personnel, often at short intervals. This may tend to prevent or compete with the personnel performing other possibly more valuable services. In addition, due to other tasks, the personnel may not always transfer tissue from one instrument to the other as soon as possible, which may potentially lead to instrument downtime, and reduced productivity or throughput.